Distictis buccinatoria is used for inflammatory‐related diseases. From a dichloromethane extract were obtained five different fractions called F1 to F5, and sub‐fractions F4‐1, F5‐1, F5‐2, and F5‐3; and were evaluated as anti‐neuroinflammatory, antioxidant, and nootropic agents in mice exposed to lipopolysaccharide. Also, were isolated herniarin, daphnoretin, and fraction's terpenes with an anti‐inflammatory activity using 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced auricular edema. The inhibition of local edema was: F1 (73.6 %), F2 (57 %), F3 (62.61 %), F4 (87.3 %), and F5 (93.57 %). Terpene fraction inhibited at 89.60 %, herniarin at 86.92 % (Emax 99.01 %, ED50 0.35 mg ear−1), and daphnoretin at 86.41 %. Fractions F4‐1 and F5‐2 (10 mg kg−1) enhancer spatial memory acquisition and spontaneous motor activity; reduced IL‐1β, TNF‐α, and IL‐6; increased IL‐10, enhanced the activity of CAT and GR. D. buccinatoria has neuroprotective activity and contains daphnoretin and herniarin, with anti‐inflammatory activity.